WO2006038223A1 - A process for preparation of 2-n-butyl -4-chloro - 1 - {[2`- (2-triphenylmethyl - 2h - tetrazole - 5- yl) - 1, 1’ - biphenyl-4-yl] methyl}-lh- imidazoie-5-methanol (intermediate of losartan) - Google Patents
A process for preparation of 2-n-butyl -4-chloro - 1 - {[2`- (2-triphenylmethyl - 2h - tetrazole - 5- yl) - 1, 1’ - biphenyl-4-yl] methyl}-lh- imidazoie-5-methanol (intermediate of losartan) Download PDFInfo
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- WO2006038223A1 WO2006038223A1 PCT/IN2005/000308 IN2005000308W WO2006038223A1 WO 2006038223 A1 WO2006038223 A1 WO 2006038223A1 IN 2005000308 W IN2005000308 W IN 2005000308W WO 2006038223 A1 WO2006038223 A1 WO 2006038223A1
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- butyl
- tetrazole
- organic layer
- biphenyl
- methanol
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
- C07D403/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings
- C07D403/10—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings linked by a carbon chain containing aromatic rings
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- the present invention relates to a process for preparation of N-substituted heterocyclic derivative,2-n-Butyl-4-chloro- 1 - ⁇ [T -(2-triphenylmethyl-2H-tetrazole-5-yl)- 1,1' -biphenyl -4-yl] methyl ⁇ -lH-imidazole-5-methanol (an intermediate of Losartan and its pharmaceutically acceptable salts).
- EP 253,310 discloses a synthetic route for the preparation of 2-n-Butyl-4- chloro- 1 - ⁇ [2 ⁇ -(2-tri ⁇ henylmethyl-2H-tetrazole-5-yl)- 1,1' -bi ⁇ henyl ⁇ 4-yl]methyl ⁇ - 1 H- imidazole-5-methanol, which involves the condensation of 2-n-Butyl-4 ⁇ chloroimidazole- 5-carboxaldehyde with 5-(4'-Bromomethyl-l,r-biphenyl-2-yl)-l-(triphenylmethyl)-lH- tetrazole in a solvent such as alcohol, DMF or DMSO, in a basic medium, for example in the presence of sodium hydroxide, sodium carbonate, potassium carbonate, triethylamine, pyridine, or a metal alcoholate such as sodium methoxide, sodium ethoxide.
- the EP 253,310 further discloses the usage of phase
- J.Med.Chem. 34 (1991) 2538 discloses a process for preparation of 2-n-Butyl-4-chloro-l- ⁇ [2' -(2-triphenylmethyl-2H-tetrazole-5-yl)- 1 , 1 '-biphenyl-4-yl] methyl ⁇ - 1 H-imidazole-5- carboxaldehyde by condensation of 2-n-Butyl-4-chloroimidazole-5-carboxaldehyde with
- Another object of the present invention is to provide a process for the preparation of 2-n- Butyl-4-chloro- 1 - ⁇ [2 ⁇ -(2-tri ⁇ henylmethyl-2H-tetrazole-5-yl)- 1,1' -biphenyl-4-yl]methyl ⁇ - lH-imidazole -5-methanol using phase transfer catalyst.
- Yet another object of the present invention is to provide a process for the preparation of 2-n-Butyl-4-chloro- 1 - ⁇ [T -(2-tri ⁇ henylmethyl-2H-tetrazole-5-yl)- 1 , r -biphenyl-4- yl]methyl ⁇ -lH-imidazole-5-methanol with improved yield.
- preparation of N-substituted heterocyclic derivative 2-n-Butyl-4-chloro- 1 - ⁇ ⁇ T ⁇ (2-triphenylmethyl-2H-tetrazole-5-yl)- 1,1' -biphenyl -4-yl]methyl ⁇ -lH-imidazole-5-methanol essentially comprises of the following steps.
- 5-(4'-Bromomethyl-l,r-biphenyl-2-yl)-l-(triphenylmethyl)-lH-tetrazole is suspended in a mixture of aqueous solution of inorganic base such as sodium hydroxide, potassium hydroxide, sodium carbonate or potassium carbonate preferably sodium hydroxide, halohydrocarbon such as methylene chloride, ethylene dichloride, propylchloride, 1- chlorobutane (n-Butylchloride) preferably 1-chlorobutane, phase transfer catalyst selectively quaternary ammonium salts such as tetrabutylammonium bromide, tetrabutyl ammonium chloride, triethylbenzyl ammonium bromide, triethylbenzyl ammonium chloride, preferably tetrabutylammonium bromide is added to the reaction mass.
- inorganic base such as sodium hydroxide, potassium hydroxide, sodium carbonate
- 2-n- Butyl-4-chloro imidazole-5-carboxaldehyde is added in single lot or in small portions to the reaction mass and mixed for about 18 hrs to 48 hrs preferably for about 24 hrs to 36 hrs at temperature of about 1O 0 C to about 65 0 C preferably at about 25 0 C to 35 0 C.
- Reaction mass is allowed to settle the layers, separated the organic layer at temperature of 35 0 C to about 6O 0 C, preferably at about 45 0 C to about 55 0 C, extracted the aqueous layer with halo hydrocarbon, washed the combined organic layer with water.
- Reaction mass is cooled to about 3O 0 C to 5O 0 C further cooled to about 2O 0 C to about 35 0 C and water is slowly added.
- Reaction mass is cooled to about O 0 C to about 2O 0 C, preferably to 5 0 C to 15 0 C over 1 hr to 4 hrs and maintained for about 2 hrs to 8 hrs at temperature of O 0 C to about 2O 0 C, preferably at about 5 0 C to about 15 0 C.
- Product is isolated by filtration, washed with chilled halohydrocarbon and dried at about 45 0 C to about 75 0 C afforded the 2-n-Butyl-4-chloro-l- ⁇ [2'-(2-triphenylmethyl-2H- tetrazole-5-yl)- 1,1' -biphenyl-4-yl]methyl ⁇ - 1 H-imidazole-5-methanol.
- the wet cake of above 2-n-Butyl-4-chloro-l- ⁇ [2'-(2-triphenylmethyl-2H- tetrazole-5-yl)-l,r-biphenyl-4-yl]methyl ⁇ -lH-imidazole-5-methanol can be recrystallized in ethyl acetate by dissolution at reflux temperature followed by cooling to about 1O 0 C to about 15 0 C affords the pure compound with a overall yield of about 70% to 80%.
- Example-1 Preparation of 2-n-Butyl-4-chloro-l- ⁇
- reaction mass is raised to 45 0 C to 5O 0 C and allowed to settle the layers.
- Organic layer is separated, extracted the aqueous layer with 1-chloro butane (200 ml) and the combined organic layer is washed with water (200ml) at 45 0 C to 50°C.
- the organic layer is cooled and sodium borohydride (7.4 g) is added at 25 0 C to 3O 0 C under nitrogen atmosphere.
- Reaction mass temperature is raised to 4O 0 C to 45 0 C, methanol (50 ml) is added over 45 min and maintained the reaction mass at 4O 0 C to 45 0 C for 5hrs.
- the wet cake (130g) is suspended in ethyl acetate (300 ml), raised the temperature to reflux, maintained for 30 min at reflux temperature. Slowly cooled the reaction mass to 15 0 C and maintained at 14 0 C to 16 0 C for 3 hrs. Filtered the product, washed with ethyl acetate (100 ml) and dried at 6O 0 C - 65 0 C till constant weight
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Abstract
The present invention relates to a process for preparation of N-substituted heterocyclic derivative,2-n-Butyl-4-chloro- 1 - { [2' -(2-triphenylmethyl-2H-tetrazole-5-yl)- 1,1' -biphenyl -4-yl] methyl} -lH-imidazole-5-methanol, an important intermediate in the synthesis of Losartan and its pharmaceutically acceptable salts using phase transfer catalyst and minimal number of solvents with improved yield.
Description
"A process for preparation of 2-n-Butyl -4-chloro - X - {\T - (2 - triphenylmethyl - 2H - tetrazole - 5- yl) - 1, 1' - biphenyI-4-yl] methyl}-lH- imidazoIe-5-methanol (intermediate of Losartan)"
The present invention relates to a process for preparation of N-substituted heterocyclic derivative,2-n-Butyl-4-chloro- 1 - { [T -(2-triphenylmethyl-2H-tetrazole-5-yl)- 1,1' -biphenyl -4-yl] methyl} -lH-imidazole-5-methanol (an intermediate of Losartan and its pharmaceutically acceptable salts).
Background of the Invention:
2-n-butyI-4-chIoro 1 - { [T -(2-methyl-2H-tetrazole-5-yl)- I5T -biphenyl-4-yl]methyl } - 1 H- imidazole-5-methanol (Losartan) has the structure as given below
Losartan
Losartan and its pharmaceutically acceptable salts are useful as antagonists of the peptide hormone angiotensin II. Angiotensin II is a potent vasopressor and the biologically active product of the rennin-angiotensin system. Thus Losartan is useful in the treatment of hypertension and congestive heart failure.
Eur. Pat. No. EP 253,310 discloses a synthetic route for the preparation of 2-n-Butyl-4- chloro- 1 -{ [2Λ-(2-triρhenylmethyl-2H-tetrazole-5-yl)- 1,1' -biρhenyl~4-yl]methyl} - 1 H- imidazole-5-methanol, which involves the condensation of 2-n-Butyl-4~chloroimidazole- 5-carboxaldehyde with 5-(4'-Bromomethyl-l,r-biphenyl-2-yl)-l-(triphenylmethyl)-lH- tetrazole in a solvent such as alcohol, DMF or DMSO, in a basic medium, for example in
the presence of sodium hydroxide, sodium carbonate, potassium carbonate, triethylamine, pyridine, or a metal alcoholate such as sodium methoxide, sodium ethoxide. The EP 253,310 further discloses the usage of phase transfer conditions in the condensation reaction.
U.S. Pat. No. 5,310,928 discloses a process for preparation of 2-n-Butyl-4-chloro-l- {[2'-
(2-triphenylmethyl-2H-tetrazole-5-yl)- 1,1' -biphenyl-4-yl] methyl} - 1 H-imidazole-5- methanol by the condensation of 2-n-Butyl-4-chloroimidazole-5-carboxaldehyde with 5- (4'-Bromomethyl-l,r-biphenyl-2-yl)-l-(triphenylmethyl)-lH-tetrazole in presence of potassium carbonate in N,N-Dimethyl acetamide as solvent followed by reduction with sodium borohydride, with or without isolation of the intermediate 2-n-Butyl-4-chloro-l- {[2'-(2-triρhenylmethyl-2H-tetrazole-5-yl)-l,r-biphenyl-4-yl]methyl}-lH-imidazole-5- carboxaldehyde and crystall- ization from butyl chloride followed by recrystallization with ethyl acetate in a overall yield of 72%.
Eur. Pat. No. EP 324,377 discloses a process for the preparation of 2-n-Butyl-4-chloro-l-
{ [2' -(2-triphenylmethyl-2H-tetrazole-5-yl)-l , 1 ' -biphenyl-4-yl]methyl} - 1 H-imidazole-5- methanol by condensation of 2-n-Butyl-4-chloroimidazole-5-carboxaldehyde with 5-(4'- Bromomethyl-l,r-biphenyl-2-yl)-l-(tri phenylmethyl)-lH-tetrazole in presence of sodium hydroxide, water, methylene dichloride, carbon tetra chloride followed by reduction with sodium borohydride, isolation by distillation of solvents, addition of toluene and dilution with ethyl acetate, n-heptane in a overall yield of 51.7%.
J.Med.Chem. 34 (1991) 2538 discloses a process for preparation of 2-n-Butyl-4-chloro-l- { [2' -(2-triphenylmethyl-2H-tetrazole-5-yl)- 1 , 1 '-biphenyl-4-yl] methyl } - 1 H-imidazole-5- carboxaldehyde by condensation of 2-n-Butyl-4-chloroimidazole-5-carboxaldehyde with
5-(4'-Bromomethyl-l,r-biphenyl-2-yl)-l-(triphenylmethyl)-lH-tetrazole in presence of a base, tetrabutyl phosphonium bromide as a phase transfer catalyst in methylene chloride and water followed by concentration and crystallization with nitromethane in a overall yield of 59.3%.
AU the above prior art processes describes the processes which involves the use of multiple solvents for the preparation, isolation and recrystallization of 2-n-Butyl-4- chloro-1- {[2'-(2-triphenyl methyl-2H-tetrazole-5-yl)-l,r-biρhenyl-4-yl]methyl}-lH- imidazole-5-methanol from 2-n-Butyl-4-chloroimidazole-5-carboxaldehyde,5-(4'- Bromomethyl-l,r-biphenyl-2-yl)-l-(triphenylmethyl -lH-tetrazole or with low yields thereby increasing the operational cost of the product.
There is a long felt need of the industry to provide a process for the preparation of 2-n- Butyl-4-chloro-l-{[2Λ-(2-triphenylmethyl-2H-tetrazole-5-yl)-l,r-biphenyl-4-yl]methyl}- lH-imidazole -5-methanol,important intermediate in the synthesis of Losartan without involving the usage of multiple solvents and with improved yield.
Summary of the Invention:
The main object of the present invention is to provide a process for the preparation of N- substituted heterocyclic derivatives
Another object of the present invention is to provide a process for the preparation of 2-n- Butyl-4-chloro- 1 - { [T -(2-triρhenylmethyl-2H-tetrazole-5-yl)- 1 , 1' -biphenyl-4-yl]methyl} - lH-imidazole -5 -methanol for its use in preparation of Losartan.
Another object of the present invention is to provide a process for preparation of 2-n- Butyl-4-chloro- 1 - { [T -(2-triphenylmethyl-2H-tetrazole-5-yl)- 1,1' -biρhenyl-4-yl]methyl} - lH-imidazole-5-methanol without using multiple solvents.
Another object of the present invention is to provide a process for the preparation of 2-n- Butyl-4-chloro- 1 - { [2Λ -(2-triρhenylmethyl-2H-tetrazole-5-yl)- 1,1' -biphenyl-4-yl]methyl } - lH-imidazole -5-methanol using phase transfer catalyst.
Yet another object of the present invention is to provide a process for the preparation of 2-n-Butyl-4-chloro- 1 - { [T -(2-triρhenylmethyl-2H-tetrazole-5-yl)- 1 , r -biphenyl-4- yl]methyl}-lH-imidazole-5-methanol with improved yield.
Accordingly in the present invention (Scheme-I) 2-n-Butyl-4-chloroimidazole-5- carboxaldehyde is condensed with 5-(4Λ-Bromo methyl- 1,1' -biphenyl-2-y I)-I - (triphenylmethyl)-lH-tetrazole in water, halohydrocarbon in presence of base, phase transfer catalyst, followed by separation of organic layer, reduction with sodium borohydride and lower alcohol, isolation of the product by addition of water, separation and concentration of the organic layer. The product can be recrystallized with ethyl acetate if necessary with an overall yield of about 80%.
Scheme-1
The prepared N-substituted heterocyclic derivatives 2-n-Butyl-4-chloro-l-{[2'-(2- triphenylmethyl-2H-tetrazole-5-yl)-l,r-biphenyl-4-yl]methyl}-lH-imidazole-5-methanol can be converted to losartan and its pharmaceutically acceptable salts by the prior art methods.
Detailed description of the Invention:
Thus in accordance with the present invention preparation of N-substituted heterocyclic derivative 2-n-Butyl-4-chloro- 1 - { \T ~(2-triphenylmethyl-2H-tetrazole-5-yl)- 1,1' -biphenyl -4-yl]methyl}-lH-imidazole-5-methanol essentially comprises of the following steps.
- Reacting 2-n-Butyl-4-chloroimidazole-5-carboxaldehyde with 5-(4'-Bromo methyl-l,r-biphenyl-2-yl)-l-(triphenylmethyl)-lH-tetrazole in a mixture of water and halohydrocarbon in presence of base and phase transfer catalyst.
- Maintaining the mass to reaction completion - Separating the aqueous layer
- Reacting the organic layer with sodium borohydride and lower alcohol
- Adding water to the reaction mass and separating the layers
- Concentrating the organic layer
- Isolating and drying the product - Recrystallizing the product (if necessary)
5-(4'-Bromomethyl-l,r-biphenyl-2-yl)-l-(triphenylmethyl)-lH-tetrazole is suspended in a mixture of aqueous solution of inorganic base such as sodium hydroxide, potassium hydroxide, sodium carbonate or potassium carbonate preferably sodium hydroxide, halohydrocarbon such as methylene chloride, ethylene dichloride, propylchloride, 1- chlorobutane (n-Butylchloride) preferably 1-chlorobutane, phase transfer catalyst selectively quaternary ammonium salts such as tetrabutylammonium bromide, tetrabutyl ammonium chloride, triethylbenzyl ammonium bromide, triethylbenzyl ammonium chloride, preferably tetrabutylammonium bromide is added to the reaction mass. 2-n- Butyl-4-chloro imidazole-5-carboxaldehyde is added in single lot or in small portions to the reaction mass and mixed for about 18 hrs to 48 hrs preferably for about 24 hrs to 36 hrs at temperature of about 1O0C to about 650C preferably at about 250C to 350C. Reaction mass is allowed to settle the layers, separated the organic layer at temperature of 350C to about 6O0C, preferably at about 450C to about 550C, extracted the aqueous layer with halo hydrocarbon, washed the combined organic layer with water.
Sodium borohydride is added to the organic layer at temperature of about 1O0C to about
450C, preferably at about 2O0C to about 350C under nitrogen atmosphere. Temperature of the reaction mass is raised to about 350C to about 550C, selectively to about 4O0C to about 5O0C, lower alcohol such as methanol, ethanol, isopropanol, propanol, preferably
methanol, ethanol is added slowly over 15 min to about 120 min and maintained the reaction mass for about 2 hrs to 8 hrs at temperature of 350C to about 550C5 preferably at about 4O0C to 5O0C. Water is added to the reaction mass, allowed to settle and separated the layers at temperature of 350C to about 550C, added additional quantity of halo hydrocarbon if required to the organic layer. Organic layer is washed with water at temperature of about 350C to about 750C, preferably at about 5O0C to about 650C, and concentrated the organic layer to about 70% to about 40% of the original volume by distillation of solvent. Reaction mass is cooled to about 3O0C to 5O0C further cooled to about 2O0C to about 350C and water is slowly added. Reaction mass is cooled to about O0C to about 2O0C, preferably to 50C to 150C over 1 hr to 4 hrs and maintained for about 2 hrs to 8 hrs at temperature of O0C to about 2O0C, preferably at about 50C to about 150C. Product is isolated by filtration, washed with chilled halohydrocarbon and dried at about 450C to about 750C afforded the 2-n-Butyl-4-chloro-l-{[2'-(2-triphenylmethyl-2H- tetrazole-5-yl)- 1,1' -biphenyl-4-yl]methyl} - 1 H-imidazole-5-methanol.
Optionally the wet cake of above 2-n-Butyl-4-chloro-l-{[2'-(2-triphenylmethyl-2H- tetrazole-5-yl)-l,r-biphenyl-4-yl]methyl}-lH-imidazole-5-methanol can be recrystallized in ethyl acetate by dissolution at reflux temperature followed by cooling to about 1O0C to about 150C affords the pure compound with a overall yield of about 70% to 80%.
The required 2-n-Butyl-4-chloroimidazole-5-carboxaldehyde and 5-(4'-Bromomethyl- l,r-biphenyl-2-yl)-l-(triphenylmethyl)-lH-tetrazole are prepared by the prior art methods.
The invention is further illustrated with the following example
Example-1: Preparation of 2-n-Butyl-4-chloro-l-{|T-(2-triphenyl methyl-2H- tetrazole-5-yl)-l,r-biphenyI-4-yl]methyl}-lH-imidazole -5-methanol.
5-(4'-Bromomethyl-l,r-biphenyl-2-yl)-l-(triphenylmethyl)-lH-tetrazole (100 g) is suspended in a mixture of 1-chlorobutane (600 ml)and IN sodium hydroxide (400 ml) at
temperature of 250C and tetra butyl ammonium bromide (1Og) is added. 2-n-Butyl-4- chloroimidazole-5-carboxaldehyde (35g) is added in small portions to the reaction mass at temperature of 250C to 3O0C and maintained the reaction mass for about 32 hrs at temperature of 250C to 3O0C. Temperature of the reaction mass is raised to 450C to 5O0C and allowed to settle the layers. Organic layer is separated, extracted the aqueous layer with 1-chloro butane (200 ml) and the combined organic layer is washed with water (200ml) at 450C to 50°C.The organic layer is cooled and sodium borohydride (7.4 g) is added at 250C to 3O0C under nitrogen atmosphere. Reaction mass temperature is raised to 4O0C to 450C, methanol (50 ml) is added over 45 min and maintained the reaction mass at 4O0C to 450C for 5hrs. Water (100 ml) is added to the reaction mass, allowed to settle and separated the layers at 4O0C to 450C. 1 -Chlorobutane (100 ml) is added to the organic layer, raised the temperature to 6O0C to 650C and washed with water (100 ml). Distilled off the solvent till reaction mass volume becomes around 600 ml. Cooled the reaction mass to 280C. Water (100 ml) is added, cooled the reaction mass to 1O0C over 2 hrs and maintained at 100C to 150C for 4 hrs. Filtered the product and washed with chilled 1- chloro butane (50 ml).
The wet cake (130g) is suspended in ethyl acetate (300 ml), raised the temperature to reflux, maintained for 30 min at reflux temperature. Slowly cooled the reaction mass to 150C and maintained at 140C to 160C for 3 hrs. Filtered the product, washed with ethyl acetate (100 ml) and dried at 6O0C - 650C till constant weight
The dry weight of 2-n-Butyl-4-chloro-l-{[2Λ-(2-triphenylmethyl-2H-tetrazole-5-yl)-l,r- biρhenyl-4-yl]methyl}-lH-imidazole-5-methanol is 93.0 g (Yield: 78%)
Claims
We claim: L A process for the preparation of N-substituted heterocyclic derivative,2-n-Butyl-4-chloro- 1 - { |T -(2-triρhenylmethyl-2H-tetrazole-5-yl)- 1,1' -biphenyl-4-yl]methyl} - 1 H-imidazole - 5 -methanol comprising steps
- Reacting 2-n-Butyl-4-chloroimidazole-5-carboxaldehyde with 5-(4'- Bromomethyl- 1,1' -biphenyl-2-yl)- 1 -(triphenylmethyl)- 1 H-tetrazole in water, halohydrocarbon in presence of base and phase transfer catalyst.
- Maintaining the reaction mass at temperature of 100C to 650C for 18 hrs to 48 hrs
- Allowing to settle and separating the layers
- Reacting the organic layer with sodium borohydride and lower alcohol
- Adding water to the reaction mass and separating the layers - Washing the organic layer with water
- Concentrating the organic layer
- Isolation and drying the product at temperature of 450C to 750C
- Recrystallizing the product (if necessary)
2. The process as claimed in claim 1, wherein base is sodium hydroxide, potassium hydroxide, sodium carbonate or potassium carbonate preferably sodium hydroxide.
3. The process as claimed in claim 1, wherein the halohydrocarbon is methylene chloride, ethylene dichloride, propyl chloride and 1-chlorobutane.
4. The process as claimed in claim 1 and 3, wherein the preferred halohydrocarbon is 1- chlorobutane.
5. The process as claimed in claim 1, wherein the phase transfer catalyst is quaternary ammonium salt.
6. The process as claimed in claim 1 & 5, wherein the phase transfer catalyst is tetrabutylammonium bromide, tetrabutyl ammonium chloride, triethylbenzyl ammonium bromide, triethyl benzylammonium chloride, preferably tetrabutyl ammonium bromide.
7. The process as claimed in claim 1 , wherein the separation of layers is carried out at temperature of 350C to 6O0C.
8. The process as claimed in claim 1, wherein the reaction of organic layer with sodium borohydride and lower alcohol is at temperature of 350C to 550C for 2 hrs to 8 hrs.
9. The process as claimed in claim 1 & 8 wherein the lower alcohol is methanol, ethanol, propanol and isopropanol.
10. The process as claimed in claim 1, wherein the washing of organic layer with water is carried out at 350C to 750C.
11. The process as claimed in claim 1, wherein the organic layer is concentrated to a volume of 40% to 70% of its original volume.
12. The process as claimed in claim 1, wherein the product is isolated at O0C to 2O0C
13. The process as claimed in claim 1, wherein recrystallization is carried out in ethyl acetate.
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| IN1032/CHE/2004 | 2004-10-06 | ||
| IN1032CH2004 | 2004-10-06 |
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| Publication Number | Publication Date |
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| WO2006038223A1 true WO2006038223A1 (en) | 2006-04-13 |
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| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| PCT/IN2005/000308 WO2006038223A1 (en) | 2004-10-06 | 2005-09-13 | A process for preparation of 2-n-butyl -4-chloro - 1 - {[2`- (2-triphenylmethyl - 2h - tetrazole - 5- yl) - 1, 1’ - biphenyl-4-yl] methyl}-lh- imidazoie-5-methanol (intermediate of losartan) |
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Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102408353A (en) * | 2011-12-16 | 2012-04-11 | 珠海润都制药股份有限公司 | Preparation method of candesartan intermediate |
| EP2502919A1 (en) * | 2009-11-17 | 2012-09-26 | Mitsubishi Tanabe Pharma Corporation | Process for production of biphenyl derivative |
Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0253310A2 (en) * | 1986-07-11 | 1988-01-20 | E.I. Du Pont De Nemours And Company | Angiotensin II receptor blocking imidazoles |
| US5130439A (en) * | 1991-11-18 | 1992-07-14 | Lo Young S | Tetrazolylphenylboronic acid intermediates for the synthesis of AII receptor antagonists |
| WO2005023758A2 (en) * | 2003-09-04 | 2005-03-17 | Bakulesh Mafatlal Khamar | Process for the preparation of losartan potassium form i |
-
2005
- 2005-09-13 WO PCT/IN2005/000308 patent/WO2006038223A1/en active Application Filing
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0253310A2 (en) * | 1986-07-11 | 1988-01-20 | E.I. Du Pont De Nemours And Company | Angiotensin II receptor blocking imidazoles |
| US5130439A (en) * | 1991-11-18 | 1992-07-14 | Lo Young S | Tetrazolylphenylboronic acid intermediates for the synthesis of AII receptor antagonists |
| WO2005023758A2 (en) * | 2003-09-04 | 2005-03-17 | Bakulesh Mafatlal Khamar | Process for the preparation of losartan potassium form i |
Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP2502919A1 (en) * | 2009-11-17 | 2012-09-26 | Mitsubishi Tanabe Pharma Corporation | Process for production of biphenyl derivative |
| EP2502919A4 (en) * | 2009-11-17 | 2013-06-26 | Mitsubishi Tanabe Pharma Corp | Process for production of biphenyl derivative |
| US8530506B2 (en) | 2009-11-17 | 2013-09-10 | Mitsubishi Tanabe Pharma Corporation | Process for production of biphenyl derivative |
| CN102408353A (en) * | 2011-12-16 | 2012-04-11 | 珠海润都制药股份有限公司 | Preparation method of candesartan intermediate |
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